Pregestational fructose-induced metabolic syndrome in Wistar rats causes sexually dimorphic behavioral changes in their offspring.

Metabolic syndrome (MetS), marked by enduring metabolic inflammation, has detrimental effects on cognitive performance and brain structure, influencing behavior. This study aimed to investigate whether maternal MetS could negatively impact the neurodevelopment and metabolism of offspring. To test this hypothesis, 2 months old female Wistar rats were subjected to a 10-week regimen of tap water alone or supplemented with 20% fructose to induce MetS. Dams were mated with healthy males to generate litters: OC (offspring from control dams) and OMetS (offspring from dams with MetS). To isolate prenatal effects, all pups were breastfed by control nurse dams, maintaining a standard diet and water ad libitum until weaning. Behavioral assessments were conducted between postnatal days (PN) 22 and 95, and metabolic parameters were analyzed post-sacrifice on PN100. Results from the elevated plus maze, the open field, and the marble burying tests revealed a heightened anxiety-like phenotype in OMetS females. The novel object recognition test showed that exclusively OMetS males had long-term memory impairment. In the reciprocal social interaction test, OMetS displayed a lower number of social interactions, with a notable increase in "socially inactive" behavior observed exclusively in females. Additionally, in the three-chamber test, social preference and social novelty indexes were found to be lower solely among OMetS females. An increase in visceral fat concomitantly with hypertriglyceridemia was the relevant postmortem metabolic finding in OMetS females. In summary, maternal MetS leads to enduring damage and adverse effects on offspring neurobehavior and metabolism, with notable sexual dimorphism.

Effects of expectation on face perception and its association with expertise.

Perceptual decisions are derived from the combination of priors and sensorial input. While priors are broadly understood to reflect experience/expertise developed over one's lifetime, the role of perceptual expertise at the individual level has seldom been directly explored. Here, we manipulate probabilistic information associated with a high and low expertise category (faces and cars respectively), while assessing individual level of expertise with each category. 67 participants learned the probabilistic association between a color cue and each target category (face/car) in a behavioural categorization task. Neural activity (EEG) was then recorded in a similar paradigm in the same participants featuring the previously learned contingencies without the explicit task. Behaviourally, perception of the higher expertise category (faces) was modulated by expectation. Specifically, we observed facilitatory and interference effects when targets were correctly or incorrectly expected, which were also associated with independently measured individual levels of face expertise. Multivariate pattern analysis of the EEG signal revealed clear effects of expectation from 100 ms post stimulus, with significant decoding of the neural response to expected vs. not stimuli, when viewing identical images. Latency of peak decoding when participants saw faces was directly associated with individual level facilitation effects in the behavioural task. The current results not only provide time sensitive evidence of expectation effects on early perception but highlight the role of higher-level expertise on forming priors.

Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes.

BACKGROUND: Obesity and type 2 diabetes are prevalent in patients with heart failure with preserved ejection fraction and are characterized by a high symptom burden. No approved therapies specifically target obesity-related heart failure with preserved ejection fraction in persons with type 2 diabetes. METHODS: We randomly assigned patients who had heart failure with preserved ejection fraction, a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more, and type 2 diabetes to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level. RESULTS: A total of 616 participants underwent randomization. The mean change in the KCCQ-CSS was 13.7 points with semaglutide and 6.4 points with placebo (estimated difference, 7.3 points; 95% confidence interval [CI], 4.1 to 10.4; P<0.001), and the mean percentage change in body weight was -9.8% with semaglutide and -3.4% with placebo (estimated difference, -6.4 percentage points; 95% CI, -7.6 to -5.2; P<0.001). The results for the confirmatory secondary end points favored semaglutide over placebo (estimated between-group difference in change in 6-minute walk distance, 14.3 m [95% CI, 3.7 to 24.9; P = 0.008]; win ratio for hierarchical composite end point, 1.58 [95% CI, 1.29 to 1.94; P<0.001]; and estimated treatment ratio for change in CRP level, 0.67 [95% CI, 0.55 to 0.80; P<0.001]). Serious adverse events were reported in 55 participants (17.7%) in the semaglutide group and 88 (28.8%) in the placebo group. CONCLUSIONS: Among patients with obesity-related heart failure with preserved ejection fraction and type 2 diabetes, semaglutide led to larger reductions in heart failure-related symptoms and physical limitations and greater weight loss than placebo at 1 year. (Funded by Novo Nordisk; STEP-HFpEF DM ClinicalTrials.gov number, NCT04916470.).

Hidden Port Site Incision for Robotic Foregut and Hepatopancreatobiliary Operation: A Cosmetically Superior Approach.

While the widespread adoption of minimally invasive surgery has led to improved cosmesis for abdominal operations, visible scars on the abdomen may still have a negative psychosocial impact on patients, especially for those with poor healing. We have developed a cosmetically favorable, safe, and easily adaptable robotic technique for common foregut and hepatopancreatobiliary procedures with hidden incisions at the level of the pubic hairline to minimize visibility. This technique monopolizes on the unique advantages of the robotic platform to maximize cosmetic outcome while maintaining clinical outcomes and technical ease. Herein we describe how to accomplish this technique for three different procedures: anti-reflux operation, distal pancreatectomy, and small bowel resection. In our experience, this technique of hiding port site incisions at the level of the pubic hairline can be easily adopted for improved patient quality of life and cosmesis. We especially recommend this technique in patients with a history of hypertrophic or keloid scars.

Randomness impacts the building of specific priors, visual exploration, and perception in object recognition.

Recognising objects is a vital skill on which humans heavily rely to respond quickly and adaptively to their environment. Yet, we lack a full understanding of the role visual information sampling plays in this process, and its relation to the individual's priors. To bridge this gap, the eye-movements of 18 adult participants were recorded during a free-viewing object-recognition task using Dots stimuli1. Participants viewed the stimuli in one of three orders: from most visible to least (Descending), least visible to most (Ascending), or in a randomised order (Random). This dictated the strength of their priors along the experiment. Visibility order influenced the participants' recognition performance and visual exploration. In addition, we found that while orders allowing for stronger priors generally led participants to visually sample more informative locations, this was not the case of Random participants. Indeed, they appeared to behave naïvely, and their use of specific object-related priors was fully impaired, while they maintained the ability to use general, task-related priors to guide their exploration. These findings have important implications for our understanding of perception, which appears to be influenced by complex cognitive processes, even at the basic level of visual sampling during object recognition.

Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials.

BACKGROUND: In the STEP-HFpEF (NCT04788511) and STEP-HFpEF DM (NCT04916470) trials, the GLP-1 receptor agonist semaglutide improved symptoms, physical limitations, bodyweight, and exercise function in people with obesity-related heart failure with preserved ejection fraction. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, we aimed to provide a more definitive assessment of the effects of semaglutide across a range of outcomes and to test whether these effects were consistent across key patient subgroups. METHODS: We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries. In both trials, eligible participants were aged 18 years or older, had heart failure with a left ventricular ejection fraction of at least 45%, a BMI of at least 30 kg/m2, New York Heart Association class II-IV symptoms, and a Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; a measure of heart failure-related symptoms and physical limitations) of less than 90 points. In STEP-HFpEF, people with diabetes or glycated haemoglobin A1c concentrations of at least 6·5% were excluded, whereas for inclusion in STEP-HFpEF DM participants had to have been diagnosed with type 2 diabetes at least 90 days before screening and to have an HbA1c of 10% or lower. In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks. The dual primary endpoints were change from baseline to week 52 in KCCQ-CSS and bodyweight in all randomly assigned participants. Confirmatory secondary endpoints included change from baseline to week 52 in 6-min walk distance, a hierarchical composite endpoint (all-cause death, heart failure events, and differences in changes in KCCQ-CSS and 6-min walk distance); and C-reactive protein (CRP) concentrations. Heterogeneity in treatment effects was assessed across subgroups of interest. We assessed safety in all participants who received at least one dose of study drug. FINDINGS: Between March 19, 2021 and March 9, 2022, 529 people were randomly assigned in STEP-HFpEF, and between June 27, 2021 and Sept 2, 2022, 616 were randomly assigned in STEP-HFpEF DM. Overall, 1145 were included in our pooled analysis, 573 in the semaglutide group and 572 in the placebo group. Improvements in KCCQ-CSS and reductions in bodyweight between baseline and week 52 were significantly greater in the semaglutide group than in the placebo group (mean between-group difference for the change from baseline to week 52 in KCCQ-CSS 7·5 points [95% CI 5·3 to 9·8]; p<0·0001; mean between-group difference in bodyweight at week 52 -8·4% [-9·2 to -7·5]; p<0·0001). For the confirmatory secondary endpoints, 6-min walk distance (mean between-group difference at week 52 17·1 metres [9·2 to 25·0]) and the hierarchical composite endpoint (win ratio 1·65 [1·42 to 1·91]) were significantly improved, and CRP concentrations (treatment ratio 0·64 [0·56 to 0·72]) were significantly reduced, in the semaglutide group compared with the placebo group (p<0·0001 for all comparisons). For the dual primary endpoints, the efficacy of semaglutide was largely consistent across multiple subgroups, including those defined by age, race, sex, BMI, systolic blood pressure, baseline CRP, and left ventricular ejection fraction. 161 serious adverse events were reported in the semaglutide group compared with 301 in the placebo group. INTERPRETATION: In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide was superior to placebo in improving heart failure-related symptoms and physical limitations, and reducing bodyweight in participants with obesity-related heart failure with preserved ejection fraction. These effects were largely consistent across patient demographic and clinical characteristics. Semaglutide was well tolerated. FUNDING: Novo Nordisk.

Performance of two modified two-tier algorithms for the serologic diagnosis of Lyme disease.

We compared the performance of a new modified two-tier testing (MTTT) platform, the Diasorin Liaison chemiluminescent immunoassay (CLIA), to the Zeus enzyme-linked immunoassay (ELISA) MTTT and to Zeus ELISA/Viramed immunoblot standard two-tier testing (STTT) algorithm. Of 537 samples included in this study, 91 (16.9%) were positive or equivocal by one or more screening tests. Among these 91 samples, only 57 samples were concordant positive by first-tier screening tests, and only 19 of 57 were concordant by the three second-tier methods. For IgM results, positive percent agreement (PPA) was 68.1% for Diasorin versus 89.4% for Zeus compared to immunoblot. By contrast, the PPA for IgG for both Diasorin and Zeus was 100%. Using a 2-out-of-3 consensus reference standard, the PPAs for IgM were 75.6%, 97.8%, and 95.6% for Diasorin, Zeus, and immunoblot, respectively. The difference between Zeus MTTT and Diasorin MTTT for IgM detection was significant (P = 0.0094). PPA for both Diasorin and Zeus MTTT IgG assays was 100% but only 65.9% for immunoblot STTT (P = 0.0005). In total, second-tier positive IgM and/or IgG results were reported for 57 samples by Diasorin MTTT, 63 by Zeus MTTT, and 54 by Viramed STTT. While Diasorin CLIA MTTT had a much more rapid, automated, and efficient workflow, Diasorin MTTT was less sensitive for the detection of IgM than Zeus MTTT and STTT including in 5 early Lyme cases that were IgM negative but IgG positive. IMPORTANCE: The laboratory diagnosis of Lyme disease relies upon the detection of antibodies to Borrelia species. Standard two tier testing (STTT) methods rely upon immunoblots which have clinical and technical limitations. Modified two-tier testing (MTTT) methods have recently become available and are being widely adopted. There are limited independent data available assessing the performance of MTTT and STTT methods.

Measurement bias in caregiver-report of early childhood behavior problems across demographic factors in an ECHO-wide diverse sample.

Background: Research and clinical practice rely heavily on caregiver-report measures, such as the Child Behavior Checklist 1.5-5 (CBCL/1.5-5), to gather information about early childhood behavior problems and to screen for child psychopathology. While studies have shown that demographic variables influence caregiver ratings of behavior problems, the extent to which the CBCL/1.5-5 functions equivalently at the item level across diverse samples is unknown. Methods: Item-level data of CBCL/1.5-5 from a large sample of young children (N = 9087) were drawn from 26 cohorts in the Environmental influences on Child Health Outcomes program. Factor analyses and the alignment method were applied to examine measurement invariance (MI) and differential item functioning (DIF) across child (age, sex, bilingual status, and neurodevelopmental disorders), and caregiver (sex, education level, household income level, depression, and language version administered) characteristics. Child race was examined in sensitivity analyses. Results: Items with the most impactful DIF across child and caregiver groupings were identified for Internalizing, Externalizing, and Total Problems. The robust item sets, excluding the high DIF items, showed good reliability and high correlation with the original Internalizing and Total Problems scales, with lower reliability for Externalizing. Language version of CBCL administration, education level and sex of the caregiver respondent showed the most significant impact on MI, followed by child age. Sensitivity analyses revealed that child race has a unique impact on DIF over and above socioeconomic status. Conclusions: The CBCL/1.5-5, a caregiver-report measure of early childhood behavior problems, showed bias across demographic groups. Robust item sets with less DIF can measure Internalizing and Total Problems equally as well as the full item sets, with slightly lower reliability for Externalizing, and can be crosswalked to the metric of the full item set, enabling calculation of normed T scores based on more robust item sets.

Metagenomic sequencing sheds light on microbes putatively associated with pneumonia-related fatalities of white-tailed deer (Odocoileus virginianus).

With emerging infectious disease outbreaks in human, domestic and wild animal populations on the rise, improvements in pathogen characterization and surveillance are paramount for the protection of human and animal health, as well as the conservation of ecologically and economically important wildlife. Genomics offers a range of suitable tools to meet these goals, with metagenomic sequencing facilitating the characterization of whole microbial communities associated with emerging and endemic disease outbreaks. Here, we use metagenomic sequencing in a case-control study to identify microbes in lung tissue associated with newly observed pneumonia-related fatalities in 34 white-tailed deer (Odocoileus virginianus) in Wisconsin, USA. We identified 20 bacterial species that occurred in more than a single individual. Of these, only Clostridium novyi was found to substantially differ (in number of detections) between case and control sample groups; however, this difference was not statistically significant. We also detected several bacterial species associated with pneumonia and/or other diseases in ruminants (Mycoplasma ovipneumoniae, Trueperella pyogenes, Pasteurella multocida, Anaplasma phagocytophilum, Fusobacterium necrophorum); however, these species did not substantially differ between case and control sample groups. On average, we detected a larger number of bacterial species in case samples than controls, supporting the potential role of polymicrobial infections in this system. Importantly, we did not detect DNA of viruses or fungi, suggesting that they are not significantly associated with pneumonia in this system. Together, these results highlight the utility of metagenomic sequencing for identifying disease-associated microbes. This preliminary list of microbes will help inform future research on pneumonia-associated fatalities of white-tailed deer.

Development and Psychometric Validation of a Patient-Reported Outcome Measure to Assess the Signs and Symptoms of Chronic Hand Eczema: The Hand Eczema Symptom Diary (HESD).

INTRODUCTION: Chronic Hand Eczema (CHE) is an inflammatory skin disease of the hands. The Hand Eczema Symptom Diary (HESD) is a new patient-reported outcome measure of worst severity of core CHE signs/symptoms. This study aimed to evaluate content and psychometric validity of the HESD. METHODS: The HESD was developed based on the literature and concept elicitation interviews. Qualitative cognitive debriefing interviews were conducted with CHE patients to assess relevance and understanding of items, response options and recall period. Psychometric properties of the HESD (item performance, dimensionality, reliability, validity, responsiveness and estimation of meaningful change thresholds) were then assessed, first using data from a phase 2b trial (NCT03683719), and confirmed using data from the first 280 participants completing the 16-week treatment phase of a phase 3 trial (NCT04871711). RESULTS: Cognitive debriefing supported item refinement and removal of items and confirmed all items were well understood and relevant to patients. Item properties and dimensionality analyses in the phase 2b data supported removal of additional items, resulting in the 6-item HESD included in the phase 3 trial. Unidimensionality was supported by inter-item correlations (all > 0.70) and Rasch analysis. Internal consistency (Cronbach's alpha = 0.96) and test-retest reliability (Intraclass Correlation Coefficient > 0.89) results were very strong. Construct validity was supported by moderate correlations with concurrent measures (0.53-0.64) and significant differences between severity groups (p < 0.001). Large effect sizes for mean change scores in participants that improved and significant differences between change groups indicated the ability to detect change. Anchor-based analyses supported within-individual responder definitions of ≥ 4-points for improvements in 7-day average HESD scores. CONCLUSION: The HESD is the first CHE-specific, patient-reported outcome measure of CHE signs/symptoms developed and validated in line with regulatory guidance. This article provides evidence of strong content validity and psychometric validity and shows improvements of ≥ 4 points on 7-day average HESD scores represent clinically meaningful, important changes. TRIAL REGISTRATION: NCT03683719, NCT04871711.

Stroke Prevention in Blunt Cerebrovascular Injury: Role of Aspirin 81 mg.

BACKGROUND: The stroke rate in blunt cerebrovascular injury (BCVI) varies from 25% without treatment to less than 8% with antithrombotic therapy. There is no consensus on the optimal management to prevent stroke BCVI. We investigated the efficacy and safety of oral Aspirin (ASA) 81 mg to prevent BCVI-related stroke compared to historically reported stroke rates with ASA 325 mg and heparin. METHODS: A single-center retrospective study included adult trauma patients who received oral ASA 81 mg for BCVI management between 2013 and 2022. Medical records were reviewed for demographic and injury characteristics, imaging findings, treatment-related complications, and outcomes. RESULTS: Eighty-four patients treated with ASA 81 mg for BCVI were identified. The mean age was 41.50 years, and 61.9% were male. The mean Injury Severity Score and Glasgow Coma Scale were 19.82 and 12.12, respectively. A total of 101 vessel injuries were identified, including vertebral artery injuries in 56.4% and carotid artery injuries in 44.6%. Traumatic brain injury was found in 42.9%, and 16.7% of patients had a solid organ injur. Biffl grade I (52.4%) injury was the most common, followed by grade II (37.6%) and grade III (4.9%). ASA 81 mg was started in the first 24 hours in 67.9% of patients, including 20 patients with traumatic brain injury and 8 with solid organ injuries. BCVI-related stroke occurred in 3 (3.5%) patients with Biffl grade II (n = 2) and III (n = 1). ASA-related complications were not identified in any patient. The mean length of stay in the hospital was 10.94 days, and 8 patients died during hospitalization due to complications of polytrauma. Follow-up with computed tomography angiography was performed in 8 (9.5%) patients, which showed improvement in 5 and a stable lesion in 3 at a mean time of 58 days after discharge. CONCLUSIONS: In the absence of clear guidelines regarding appropriate medication, BCVI management should be individualized case-by-case through a multidisciplinary approach. ASA 81 mg is a viable option for BCVI-related stroke prevention compared to the reported stroke rates (2%-8%) with commonly used antithrombotics like heparin and ASA 325 mg. Future prospective studies are needed to provide insight into the safety and efficacy of the current commonly used agent in managing BCVI.

Large Neutral Amino Acids Moderate the Effects of Metabolic Syndrome on Cognitive Performance in Middle-Aged Adults.

Introduction Two large neutral amino acids (LNAA), tryptophan and tyrosine, are precursors to cerebral neurotransmitters and are involved in cognitive function. Higher levels of LNAA in young adults are associated with improved cognition, although these associations appear to reverse over time. Given that exposure to metabolic syndrome (MetS) may induce premature cognitive aging, the current project aims to fill the gap in the literature by examining the effect of LNAA on cognitive performance in midlife adults with metabolic risks. Methods Eighty-eight adults, ages 40-61 years, participated in this cross-sectional study. LNAA metabolites were quantified, MetS components were measured using high-performance liquid chromatography, and MetS components were assessed in the laboratory. Composite verbal memory and executive functioning scores were computed using principal component analysis. We used linear regression models to test the interaction between LNAA and MetS while covarying for sex, age, and education. Results The kynurenine/tryptophan ratio (KTR) moderated the relation between MetS and verbal memory, even after adjusting for relevant covariates. Tyrosine metabolites were not significant moderators of the association between MetS and executive functioning. Conclusion Our findings suggest that the detected weaker memory performance in adults with a high number of MetS components may be related to relative tryptophan depletion and possible decreases in serotonin production. Further investigation is warranted to examine the potential role of LNAA in associations between cognitive performance and metabolic risks over time.

FGF21 protects against ischaemia reperfusion injury in normal and fatty livers.

BACKGROUND: Liver ischaemia/reperfusion (I/R) injury, which is an inevitable clinical problem of liver resection, liver transplantation and haemorrhagic shock. Fibroblast growth factor 21 (FGF21) was intimately coupled with multiple metabolic processes and proved to protect against apoptosis and inflammatory response in hepatocytes during hepatic I/R injury. However, the regulatory mechanisms of FGF21 in hepatic I/R injury remains unknown. Therefore, we hypothesize that FGF21 protects hepatic tissues from I/R injury. METHODS: Blood samples were available from haemangiomas patients undergoing hepatectomy and murine liver I/R model and used to further evaluate the serum levels of FGF21 both in humans and mice. We further explored the regulatory mechanisms of FGF21 in murine liver I/R model by using FGF21-knockout mice (FGF21-KO mice) and FGF21-overexpression transgenic mice (FGF21-OE mice) fed a high-fat or ketogenic diet. RESULTS: Our results show that the circulating levels of FGF21 were robustly decreased after liver I/R in both humans and mice. Silencing FGF21 expression with FGF21-KO mice aggravates liver injury at 6 h after 75 min of partial liver ischaemia, while FGF21-OE mice display alleviated hepatic I/R injury and inflammatory response. Compared with chow diet mice, exogenous FGF21 decreases the levels of aminotransferase, histological changes, apoptosis and inflammatory response in hepatic I/R injury treatment mice with a high-fat diet. Meanwhile, ketogenic diet mice are not sensitive to hepatic I/R injury. CONCLUSIONS: The circulating contents of FGF21 are decreased during liver warm I/R injury and exogenous FGF21 exerts hepatoprotective effects on hepatic I/R injury. Thus, FGF21 regulates hepatic I/R injury and may be a key therapeutic target.

Harnessing AI to unmask Copenhagen's invisible air pollutants: A study on three ultrafine particle metrics.

Ultrafine particles (UFPs) are airborne particles with a diameter of less than 100 nm. They are emitted from various sources, such as traffic, combustion, and industrial processes, and can have adverse effects on human health. Long-term mean ambient average particle size (APS) in the UFP range varies over space within cities, with locations near UFP sources having typically smaller APS. Spatial models for lung deposited surface area (LDSA) within urban areas are limited and currently there is no model for APS in any European city. We collected particle number concentration (PNC), LDSA, and APS data over one-year monitoring campaign from May 2021 to May 2022 across 27 locations and estimated annual mean in Copenhagen, Denmark, and obtained additionally annual mean PNC data from 6 state-owned continuous monitors. We developed 94 predictor variables, and machine learning models (random forest and bagged tree) were developed for PNC, LDSA, and APS. The annual mean PNC, LDSA, and APS were, respectively, 5523 pt/cm3, 12.0 µm2/cm3, and 46.1 nm. The final R2 values by random forest (RF) model were 0.93 for PNC, 0.88 for LDSA, and 0.85 for APS. The 10-fold, repeated 10-times cross-validation R2 values were 0.65, 0.67, and 0.60 for PNC, LDSA, and APS, respectively. The root mean square error for final RF models were 296 pt/cm3, 0.48 µm2/cm3, and 1.60 nm for PNC, LDSA, and APS, respectively. Traffic-related variables, such as length of major roads within buffers 100-150 m and distance to streets with various speed limits were amongst the highly-ranked predictors for our models. Overall, our ML models achieved high R2 values and low errors, providing insights into UFP exposure in a European city where average PNC is quite low. These hyperlocal predictions can be used to study health effects of UFPs in the Danish Capital.

Association between Large Neutral Amino Acids and Brain Integrity in Middle-Aged Adults at Metabolic Risk.

This investigation delves into the interplay between large neutral amino acids (LNAA) and metabolic syndrome (MetS) in midlife adults, examining their collective influence on brain structure and cognitive function. While LNAA, such as tryptophan and phenylalanine, are known to bolster cognition in youth, our study hypothesizes a reversal of these benefits in older adults with MetS, potentially signaling premature cognitive aging. Eighty participants between 40-61 years underwent MetS component quantification, LNAA measurement via high-performance liquid chromatography, and brain imaging to evaluate white matter hyperintensity (WMH) volume and medial temporal lobe (MTL) cortical thickness. Our linear regression analysis, adjusting for sex, age, and education, revealed that phenylalanine levels moderated the relationship between MetS and WMH volume (F(6, 69) = 3.134, p < 0.05, R2 = 0.214), suggesting that MetS's cognitive impact may be partly due to phenylalanine catabolism byproducts. However, LNAA metabolites did not significantly modulate the MetS-MTL cortical thickness relationship. The findings suggest that LNAA metabolic dysregulation, marked by elevated levels in the presence of MetS, could correlate with brain structural compromises, particularly in the form of MTL cortical thinning and increased WMH load, detectable in midlife. This nuanced understanding of LNAA's role in cognitive health amid cardiovascular risk factors is pivotal, proposing a potential biomarker for early intervention. Further research is crucial to elucidate the longitudinal influence of LNAA and MetS on brain health, thereby informing strategies to mitigate cognitive decline.

Hand eczema-related presenteeism and sickness absence: A cross-sectional population-based study.

BACKGROUND: To date, hand eczema (HE)-related presenteeism has never been assessed within the general population, and general population-based studies on HE-related sickness absence are limited. OBJECTIVES: To assess the prevalence of HE-related presenteeism and sickness absence, and factors associated with HE-related presenteeism, within the Dutch general population. METHODS: Within the Lifelines Cohort Study, participants with HE in the last year (aged 18-65 in 2020), were identified by a questionnaire including questions regarding HE-related presenteeism and sickness absence. Socio-demographic factors were collected from 2006 to 2020. RESULTS: Out of the 3.703 included participants with HE, 2.7% (n = 100) reported HE-related presenteeism, with 19.8% (n = 57) among those with severe-to-very-severe HE. HE-related sickness absence was reported by 0.5% (n = 20) and 5.9% (n = 17), respectively. Logistic regression analyses, adjusted for age and sex, showed negative associations between HE-related presenteeism and higher educational attainment, higher income (>€2500) and higher occupational skill level, and positive associations for high-risk occupations, chronic HE, moderate and severe-to-very-severe HE (compared to almost clear), atopic dermatitis and occupational wet exposure. CONCLUSIONS: A high prevalence of HE-related presenteeism was found among participants with severe-to-very-severe HE. Future studies should focus on longitudinal associations with the clinical course of HE, as HE-related presenteeism might aggravate symptoms of HE.

Soil macrofauna communities in Brazilian land-use systems.

Background: Soil animal communities include more than 40 higher-order taxa, representing over 23% of all described species. These animals have a wide range of feeding sources and contribute to several important soil functions and ecosystem services. Although many studies have assessed macroinvertebrate communities in Brazil, few of them have been published in journals and even fewer have made the data openly available for consultation and further use. As part of ongoing efforts to synthesise the global soil macrofauna communities and to increase the amount of openly-accessible data in GBIF and other repositories related to soil biodiversity, the present paper provides links to 29 soil macroinvertebrate datasets covering 42 soil fauna taxa, collected in various land-use systems in Brazil. A total of 83,085 georeferenced occurrences of these taxa are presented, based on quantitative estimates performed using a standardised sampling method commonly adopted worldwide to collect soil macrofauna populations, i.e. the TSBF (Tropical Soil Biology and Fertility Programme) protocol. This consists of digging soil monoliths of 25 x 25 cm area, with handsorting of the macroinvertebrates visible to the naked eye from the surface litter and from within the soil, typically in the upper 0-20 cm layer (but sometimes shallower, i.e. top 0-10 cm or deeper to 0-40 cm, depending on the site). The land-use systems included anthropogenic sites managed with agricultural systems (e.g. pastures, annual and perennial crops, agroforestry), as well as planted forests and native vegetation located mostly in the southern Brazilian State of Paraná (96 sites), with a few additional sites in the neighbouring states of São Paulo (21 sites) and Santa Catarina (five sites). Important metadata on soil properties, particularly soil chemical parameters (mainly pH, C, P, Ca, K, Mg, Al contents, exchangeable acidity, Cation Exchange Capacity, Base Saturation and, infrequently, total N), particle size distribution (mainly % sand, silt and clay) and, infrequently, soil moisture and bulk density, as well as on human management practices (land use and vegetation cover) are provided. These data will be particularly useful for those interested in estimating land-use change impacts on soil biodiversity and its implications for below-ground foodwebs, ecosystem functioning and ecosystem service delivery. New information: Quantitative estimates are provided for 42 soil animal taxa, for two biodiversity hotspots: the Brazilian Atlantic Forest and Cerrado biomes. Data are provided at the individual monolith level, representing sampling events ranging from February 2001 up to September 2016 in 122 sampling sites and over 1800 samples, for a total of 83,085 ocurrences.

Real-world Experience of Abrocitinib Treatment in Patients with Atopic Dermatitis and Hand Eczema: Up to 28-week Results from the BioDay Registry.

Limited daily practice data on the effect of abrocitinib in patients with atopic dermatitis are available. The aim of this multicentre prospective study is to evaluate the effectiveness and safety of abrocitinib in patients with atopic dermatitis treated in daily practice. In a subgroup, the effectiveness of abrocitinib on hand eczema was evaluated. A total of 103 patients from the BioDay registry were included in the study: week 4 (n = 95), week 16 (n = 61) and week 28 (n = 39). At week 28, the Eczema Area and Severity Index (EASI)-50/75/90 was achieved by 81.8%, 57.6%, and 18.2%, respectively, and the weekly average pruritus numerical rating scale ≤ 4 by 62.9%. The effectiveness of abrocitinib was not significantly different between dupilumab non-responders and dupilumab-naïve patients/responders, and between upadacitinib non-responders and upadacitinib-naïve patients/responders. Mean ± standard deviation Hand Eczema Severity Index decreased from 27.4 ± 27.7 at baseline to 7.7 ± 12.1 at week 28 (n = 31). Thirty-two patients (31.1%) discontinued treatment due to ineffectiveness (n = 17), adverse events (n = 9) or both (n = 3). The most frequently reported adverse event was nausea (n = 28). In conclusion, abrocitinib is an effective treatment for atopic dermatitis and can be effective for patients with previous inadequate response to dupilumab or upadacitinib. Furthermore, hand eczema can improve in patients treated with abrocitinib for atopic dermatitis.